Spectroscopic studies of protein folding in membranes promise to yield new insights into the folding, aggregation, insertion and assembly mechanisms of a typical membrane protein. The combined measurements of fluorescence energy transfer kinetics and vibrational spectra will provide knowledge of population heterogeneity, internuclear distances, structural evolution, and molecular microenvironments as a folding reaction progresses. Not only will these studies elucidate the correct folding pathway for the formation of a single unique, functional transmembrane protein, but they will also shed light on misfolding and aggregation pathways that are linked to a number of common human diseases, such as cystic fibrosis and diabetes. Additionally, these proposed studies are closely linked to the molecular mechanism by which pathogens invade cells since the first step in infection is the insertion of viral/bacterial proteins into a cell membrane. Therefore, the proposed research plan will directly impact the understanding of cell attack by pathogens such as the influenza virus, the anthrax toxin and staphylococcus proteins. Finally, because a large fraction of pharmaceutical drugs are targeted towards membrane proteins, a mechanistic understanding of the folding and final assembly of these proteins will assist in the effort to design new and more effective drugs and antibiotics.